Paratuberculosis is a chronic intestinal infection in ruminants, caused by Mycobacterium avium subspecies paratuberculosis (Map). To study the role of host genetics in disease susceptibility 9 candidate genes (Toll-like receptors 2 and 6, Interleukin-10, Interleukin-12p35, Interleukin-12p40, Interleukin-12 receptor β1, Interferon-γ , Interferon-γ receptor 1, and NOD2/CARD15) selected for their potential role in immunity to mycobacterial infections were analysed for single nucleotide polymorphisms (SNP) and disease association.

For SNP discovery and disease association, a case-control study including 24 cows from farms with paratuberculosis was conducted. Sequence analysis of the 9 candidate genes from 12 paratuberculosis infected animals, and 12 age-matched healthy herd-mates, revealed 35 different SNP. The TLR2-1903T/C SNP was significantly associated with resistance to Map. This and 11 additional SNP were studied in a subsequent cohort study with 553 cows from farms with paratuberculosis. The allelic distribution of the TLR2-1903 T/C SNP was confirmed, and the TLR2-385 T/G SNP was also found to be significantly different between the infected and non-infected animals. In in vitro functional assays, ligand binding by the TLR2 of the resistant haplotype induced higher in vitro NFkB production as compared to the TLR2 of the susceptible haplotype. These findings suggest that higher activity may contribute to enhanced cell activation and a lower susceptibility to paratuberculosis.

In conclusion these data support previous work indicating a role for host genetics in susceptibility to bovine paratuberculosis, and the current study specifically identified the diversity in the TLR2 gene in the cattle population to be involved in resistance to bovine paratuberculosis.